Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinemia J84.0

Immunodeficiency-100 and with pulmonary alveolar proteinosis and hypogammaglobulinemia (IMD100) is caused by a heterozygous mutation in the OAS1 gene (164350) on chromosome 12q24.

Pathogenetically, disease symptoms are related to abnormal function of alveolar macrophages leading to decreased degradation of surfactant (Cho et al. 2018). Magg et al. (2021) noted that the disease results from a gain-of-function effect that particularly affects B cells and monocytes.

The development of the disease appears to be influenced or triggered by viral infection and is manifested by progressive respiratory failure, confluent consolidations in lung imaging, and diffuse accumulations of periodic acid-Schiff (PAS)-positive material in alveoli associated with small and non-foamy alveolar macrophages.

Immunodeficiency manifests primarily as pulmonary disease characterized by the onset of respiratory insufficiency due to pulmonary alveolar proteinosis (see Pulmonary Alveolar Proteinosis below) in the first months of life. Affected individuals may have normal respiratory function at birth.

In addition to progressive respiratory failure, patients also present with hypogammaglobulinemia, leukocytosis, and splenomegaly.

Hematopoietic stem cell transplantation (HSCT) can lead to a cure.

Many patients die in infancy or early childhood from respiratory failure

1. Cho K et al. (2006) Successful treatment of congenital pulmonary alveolar proteinosis with intravenous immunoglobulin G administration. Respirology 11: 74-77.
2. Cho K et al (2018) Heterozygous mutations in OAS1 cause infantile-onset pulmonary alveolar proteinosis with hypogammaglobulinemia. Am J Hum Genet 102: 480-486.
3. Magg T et al (2021) Heterozygous OAS1 gain-of-function variants cause an autoinflammatory immunodeficiency. Sci Imm 6: eabf9564.
4. Tanaka-Kubota M et al (2018) Hematopoietic stem cell transplantation for pulmonary alveolar proteinosis associated with primary immunodeficiency disease. Int J Hemat 107: 610-614.